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idr0171-study.txt
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123 lines (102 loc) · 11.1 KB
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# FILL IN AS MUCH INFORMATION AS YOU CAN. HINTS HAVE BEEN PUT IN SOME FIELDS AFTER THE HASH # SYMBOL. REPLACE THE HINT WITH TEXT WHERE APPROPRIATE.
# STUDY DESCRIPTION SECTION
# Section with generic information about the study including title, description, publication details (if applicable) and contact details
Comment[IDR Study Accession] idr0171
Study Title Interdisciplinary Study on Drug-Induced-Phospholipidosis of Repurposing Libraries through Machine Learning and Experimental Evaluation in Different Cell Lines
Study Type high content screen
Study Type Term Source REF EFO
Study Type Term Accession EFO_0007550
Study Description Phospholipidosis (PLD) is a cellular adverse effect that is, among others, caused by numerous cationic amphiphilic drugs. Interest is raised within pharma discovery to predict this phenomenon, as it can impact the outcome of phenotypic cellular screens and significantly delay drug development processes. The development of accurate and validated machine learning models for predicting drug-induced PLD across different cell lines and research centers could provide a valuable early application tool for the pharmaceutical industry, potentially accelerating drug discovery and reducing the risk of late-stage failures. We report here the assembly, curation, testing and modeling of one of the largest datasets of repurposed drugs (5000+) tested for PLD induction on different cell lines. A machine-learning classification method was developed and validated to predict whether molecules are prone to induce PLD effects when applied in cell-based screens.
Study Key Words Phospholipidosis Drug repurposing Machine learning
Study Organism Chlorocebus aethiops
Study Organism Term Source REF NCBITaxon
Study Organism Term Accession 9534
Study Screens Number 1
Study External URL
Study BioImage Archive Accession S-BIAD2282
Study Public Release Date 2026-03-30
# Study Publication
Study PubMed ID
Study Publication Title Experimental and machine learning-based exploration of repurposed drugs reveals chemical features underlying phospholipidosis
Study Author List Kuzikov M, Kalman A, Karki R, Reinshagen J, Huchting J, Qian K, Axelsson H, Tampere M, Östling P, Seashore-Ludlow B, Gadiya Y, Gribbon P, Zaliani A
Study PMC ID
Study DOI https://doi.org/10.1016/j.patter.2025.101453
# Study Contacts
Study Person Last Name Kuzikov
Study Person First Name Maria
Study Person Email maria.kuzikov@itmp.fraunhofer.de
Study Person Address Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany
Study Person ORCID 0000-0001-8771-1865
Study Person Roles submitter
# Study License and Data DOI
Study License CC BY 4.0
Study License URL https://creativecommons.org/licenses/by/4.0/
Study Copyright Kuzikov et al
Study Data Publisher University of Dundee
Study Data DOI https://doi.org/10.17867/10000212
Term Source Name NCBITaxon EFO CMPO Fbbi
Term Source File http://purl.obolibrary.org/obo/ http://www.ebi.ac.uk/efo/ http://www.ebi.ac.uk/cmpo/ http://purl.obolibrary.org/obo/
# SCREEN SECTION
# Screen Section containing all information relative to each screen in the study including materials used, protocols names and description, phenotype names and description.
# For multiple screens this section should be repeated. Copy and paste the whole section below and fill out for the next screen.
Screen Number 1
Comment[IDR Screen Name] idr0171-kuzikov-remedi4all/screenA
Screen Sample Type cell
Screen Description Vero E-6 kidney cells treated with repurposed drugs for phospholipidosis induction.
Screen Size Plates: 4D Images: 30,880 Planes: Average Image Dimension (XYZCT): 1080 x 1080 x 1 x 3 x 1 Total Tb: raw .tif files (200GB), ome.zarr (265.6GB).
Screen Example Images Plate: ESP0029359 Well: F5 Position: 4
Screen Imaging Method spinning disk confocal microscopy
Screen Imaging Method Term Source REF Fbbi
Screen Imaging Method Term Accession FBbi_00000253
Screen Technology Type compound screen
Screen Technology Type Term Source REF EFO
Screen Technology Type Term Accession EFO_0007553
Screen Type primary screen
Screen Type Term Source REF EFO
Screen Type Term Accession EFO_0007556
Screen Organism
Screen Organism Term Source REF NCBITaxon
Screen Organism Term Accession
Screen Comments Plate ESP0029359 has a missing image on A23 position 3 due to a focus error.
# Library section. The library file should be supplied separately and it should contain the reagents description including, at the absolute minimum: reagent ID, sequences and position in the layout (= plate + position in the plate)
Library File Name idr0171-screenA-annotation
Library File Format tab-delimited text
Library Type compound library
Library Type Term Source REF EFO
Library Type Term Accession EFO_0007569
Library Manufacturer Fraunhofer ITMP
Library Version Published on Zenodo as supplementary material https://doi.org/10.5281/zenodo.17200736
Library Experimental Conditions
Library Experimental Conditions Term Source REF EFO
Library Experimental Conditions Term Accession
Quality Control Description Positive controls with Amiodarone at 10µm and negative control with DMSO at 0.1% v/validated.
# Protocols
Protocol Name growth protocol treatment protocol HCS library protocol HCS image acquisition and feature extraction protocol HCS data analysis protocol
Protocol Type growth protocol treatment protocol HCS library protocol HCS image acquisition and feature extraction protocol HCS data analysis protocol
Protocol Type Term Source REF EFO EFO EFO EFO EFO
Protocol Type Term Accession EFO_0003789 EFO_0003969 EFO_0007571 EFO_0007572 EFO_0007573
Protocol Description Vero-E6 cells were cultured in a complete medium: Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% FBS, 6 mM L-glutamine, and 1% penicillin/streptomycin. Cells were harvested at 80% confluence from a T175 cm² flask by washing once with 10 mL of RT PBS, followed by incubation with 5 mL of Trypsin 0.05% / EDTA 0.02% for 5 minutes. Cells were then resuspended in 10 mL of prewarmed culture medium. For plating, Vero-E6 cells were diluted to a concentration of 500,000 cells/mL in cell culture medium supplemented with 1:1000 dilution of HCS LipidTOX™ Red Phospholipidosis Detection Reagent (1000X). A volume of 20 µL of this cell suspension was added to each well of the 384-well plate, and cells were incubated for 24 hours at 37 °C in a 5% CO₂ environment. For fixation, 20 µL of 8% formaldehyde solution was added to each well and incubated for 30 minutes at room temperature. After incubation, the fixation buffer was then removed, and cells were washed with 50 µL/well of PBS. Cells were stained for 45 minutes with 20 µL/well of a solution containing CellMask™ Deep Red stain (1:3,000, Invitrogen #H32721) and Hoechst 33258 (1:10,000, Merck/Sigma-Aldrich #94403) diluted in PBS. Following staining, the solution was removed, and cells were washed three times with 50 µL/well of PBS. Compounds (at 10 µM concentration) and controls (amiodarone 10 µM concentration; DMSO 0.1 v/v %) were added to clear bottom, 384-well plates (PhenoPlate 384-well, black, optically clear flat-bottom, tissue-culture treated, Revvity #6057302) using the Echo Liquid Handler (Labcyte). Image acquisition was performed using the automated Operetta Phenix High Content Screening system (Revvity). Image analysis was performed using Columbus 2.9 image analysis software (PerkinElmer Inc). Results were normalized against the positive control (amiodarone at 10 µM, set at 100% PLD induction) and the negative control (DMSO at 0.1% v/v, set at 0% PLD induction). Compounds with >50% PLD induction were classified as primary hits.
# Phenotypes
Phenotype Name phospholipidosis
Phenotype Description Compounds with >50% PLD induction were classified as primary hits.
Phenotype Score Type
Phenotype Term Source REF CMPO
Phenotype Term Name
Phenotype Term Accession
# Raw Data Files
Raw Image Data Format ome-zarr
Raw Image Organization 16 plates, 384 wells each, 5 fields per well
# Feature Level Data Files
Feature Level Data File Name idr0171-screenA-annotation
Feature Level Data File Format tab-delimited text
Feature Level Data Column Name Plate Well Characteristics [Organism] Term Source 1 REF Term Source 1 Accession Characteristics [Cell Line] Term Source 2 REF Term Source 2 Accession Compound name CHEMBL Broad_ID InChI Key SMILES PubChemURL control type Channels Nuclei - count Effect [%] Viability [%]
Feature Level Data Column Description N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A Describes the used dyes/stainings and what the fluorophores bind to Describes the well-average of counted nuclei Describes the normalized induced phospholipidosis effect Describes the well-average of observed viability of cells
# Processed Data Files
Processed Data File Name
Processed Data File Format tab-delimited text
Processed Data File Description
Processed Data Column Name
Processed Data Column Type
Processed Data Column Annotation Level
Processed Data Column Description
Processed Data Column Link To Library File